Employing a variety of in vivo and in vitro techniques, the Environmental Immunology and Neurobiology Section studies the adverse effects on the immune and nervous systems resulting from occupational, inadvertent, or therapeutic exposure to drugs, environmental chemicals, and biological materials. The ongoing objectives include efforts: (1) to evaluate and examine the influence of selected drugs (e.g. AIDS therapeutics) or environmental agents on the immune response and relate alterations in immunological functions with general and specific organ toxicity as well as altered host resistance following challenge with tumor cells or infectious agents; (2) to examine potential mechanisms of action at the cellular and molecular levels; (3) to refine and validate immune and host resistance procedures in order to better define immunotoxic endpoints; and (4) study the role of inflammatory cytokines and nuclear transcription factors in toxic responses employing both in vitro and in vivo models. General methodology employed includes various cell and tissue culture procedures, quantitative PCR, transgenic animal models, flow cytometry, electrophoresis (northern and western blots), hematological procedures and biochemical tests to determine the activity of immune and cytokine producing/responsive cells. Studies have been conducted in the following areas: (a) Development and utilization of model systems which allow assessment of skin immunity [i.e., keratinocytes]. Endpoints for these assessments include production of soluble mediators (cytokines), surface markers and effector cell function; (b) Implementation of a model system to examine the participation of cytokines in chemical-induced hepatotoxicity and lung toxicity; (c) Examining the control of cytochrome P450c and the TCDD- inducible or tumor associated aldehyde dehydrogenase in selected immune cells and their modulation by cytokines; and (d) studies to examine the role of nutrition on immunotoxicology/inflammatory endpoints.